The present invention relates to novel compounds, compositions, and methods for the treatment of psychiatric disorders and neurological diseases, including major depression, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders, as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress. In particular, the present invention relates to novel imidazopyrimidines and imidazopyridines, pharmaceutical compositions containing such compounds and their use in treating psychiatric disorders, neurological diseases, immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.
Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC)xe2x80x94derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)].
Clinical data provide evidence that CRF has a role in sychiatric disorders and neurological diseases including depression, anxiety-related disorders and feeding disorders. A role for CRF has also been postulated in the etiology and pathophysiology of Alzheimer""s disease, Parkinson""s disease, Huntington""s disease, progressive supranuclear palsy and amyotrophic lateral sclerosis as they relate to the dysfunction of CRF neurons in the central nervous system [for review see E. B. De Souza, Hosp. Practice 23:59 (1988)].
In affective disorder, or major depression, the concentration of CRF is significantly increased in the cerebral spinal fluid (CSF) of drug-free individuals [C. B. Nemeroff et al., Science 226:1342 (1984); C. M. Banki et al., Am. J. Psychiatry 144:873 (1987); R. D. France et al., Biol. Psychiatry 28:86 (1988); M. Arato et al., Biol Psychiatry 25:355 (1989)]. Furthermore, the density of CRF receptors is significantly decreased in the frontal cortex of suicide victims, consistent with a hypersecretion of CRF [C. B. Nemeroff et al., Arch. Gen. Psychiatry 45:577 (1988)]. In addition, there is a blunted adrenocorticotropin (ACTH) response to CRF (i.v. administered) observed in depressed patients [P. W. Gold et al., Am J. Psychiatry 141:619 (1984); F. Holsboer et al., Psychoneuroendocrinology 9:147 (1984); P. W. Gold et al., New Eng. J. Med. 314:1129 (1986)]. Preclinical studies in rats and non-human primates provide additional support for the hypothesis that hypersecretion of CRF may be involved in the symptoms seen in human depression [R. M. Sapolsky, Arch. Gen. Psychiatry 46:1047 (1989)]. There is preliminary evidence that tricyclic antidepressants can alter CRF levels and thus modulate the numbers of CRF receptors in brain [Grigoriadis et al., Neuropsychopharmacology 2:53 (1989)].
It has also been postulated that CRF has a role in the etiology of anxiety-related disorders. CRF produces anxiogenic effects in animals and interactions between benzodiazepine/non-benzodiazepine anxiolytics and CRF have been demonstrated in a variety of behavioral anxiety models [D. R. Britton et al., Life Sci. 31:363 (1982); C. W. Berridge and A. J. Dunn Regul. Peptides 16:83 (1986)]. Preliminary studies using the putative CRF receptor antagonist a-helical ovine CRF (9-41) in a variety of behavioral paradigms demonstrate that the antagonist produces xe2x80x9canxiolytic-likexe2x80x9d effects that are qualitatively similar to the benzodiazepines [C. W. Berridge and A. J. Dunn Horm. Behav. 21:393 (1987), Brain Research Reviews 15:71 (1990)].
Neurochemical, endocrine and receptor binding studies have all demonstrated interactions between CRF and benzodiazepine anxiolytics, providing further evidence for the involvement of CRF in these disorders. Chlordiazepoxide attenuates the xe2x80x9canxiogenicxe2x80x9d effects of CRF in both the conflict test [K. T. Britton et al., Psychopharmacology 86:170 (1985); K. T. Britton et al., Psychopharmacology 94:306 (1988)] and in the acoustic startle test [N. R. Swerdlow et al., Psychopharmacology 88:147 (1986)] in rats.
The benzodiazepine receptor antagonist (Ro15-1788), which was without behavioral activity alone in the operant conflict test, reversed the effects of CRF in a dose-dependent manner while the benzodiazepine inverse agonist (FG7142) enhanced the actions of CRF [K. T. Britton et al., Psychopharmacology 94:306 (1988)].
It has been further postulated that CRF has a role in immunological, cardiovascular or heart-related diseases such as hypertension, tachycardia and congestive heart failure, stroke, osteoporosis, premature birth, psychosocial dwarfism, stress-induced fever, ulcer, diarrhea, post-operative ileus and colonic hypersensitivity associated with psychopathological disturbance and stress.
The mechanisms and sites of action through which the standard anxiolytics and antidepressants produce their therapeutic effects remain to be elucidated. It has been hypothesized however, that they are involved in the suppression of the CRF hypersecretion that is observed in these disorders. Of particular interest is that preliminary studies examining the effects of a CRF receptor antagonist (a-helical CRF9-41) in a variety of behavioral paradigms have demonstrated that the CRF antagonist produces xe2x80x9canxiolytic-likexe2x80x9d effects qualitatively similar to the benzodiazepines (for review see G. F. Koob and K. T. Britton, In: Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide, E. B. De Souza and C. B. Nemeroff eds., CRC Press p221 (1990)).
DuPont Merck PCT application US94/11050 describes corticotropin releasing factor antagonist compounds of the formula: 
and their use to treat psychiatric disorders and neurological diseases. Included in the description are fused pyridines and pyrimidines of the formula: 
where: V is CR1a or N; Z is CR2 or N; A is CR3O or N; and D is CR2 or N.
Other compounds reported to have activity as corticotropin releasing factors are disclosed in WO 95/33750, WO 95/34563 and WO 95/33727.
In accordance with one aspect, the present invention provides novel compounds which bind to corticotropin releasing factor receptors, thereby altering the anxiogenic effects of CRF secretion. The compounds of the present invention are useful for the treatment of psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.
According to another aspect, the present invention provides novel compounds of formula (I) (described below) which are useful as antagonists of the corticotropin releasing factor. The compounds of the present invention exhibit activity as corticotropin releasing factor antagonists and appear to suppress CRF hypersecretion. The present invention also includes pharmaceutical compositions containing such compounds of formula (I), and methods of using such compounds for the suppression of CRF hypersecretion, and/or for the treatment of anxiogenic disorders.
According to yet another aspect, the present invention provides novel compounds, pharmaceutical compositions and methods which may be used in the treatment of affective disorder, anxiety, depression, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer""s disease, gastrointestinal disease, anorexia nervosa or other feeding disorder, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorder, fertility problems, disorders, the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, or a disorder selected from inflammatory disorders such as rheumatoid arthritis and osteoarthritis, pain, asthma, psoriasis and allergies; generalized anxiety disorder; panic, phobias, obsessive-compulsive disorder; post-traumatic stress disorder; sleep disorders induced by stress; pain perception such as fibromyalgia; mood disorders such as depression, including major depression, single episode depression, recurrent depression, child abuse induced depression, and postpartum depression; in dysthemia; bipolar disorders; cyclothymia; fatigue syndrome; stress-induced headache; cancer, human immunodeficiency virus (HIV) infections; neurodegenerative diseases such as Alzheimer""s disease, Parkinson""s disease and Huntington""s disease; gastrointestinal diseases such as ulcers, irritable bowel syndrome, Crohn""s disease, spastic colon, diarrhea, and post operative ilius and colonic hypersensitivity associated by psychopathological disturbances or stress; eating disorders such as anorexia and bulimia nervosa; hemorrhagic stress; stress-induced psychotic episodes; euthyroid sick syndrome; syndrome of inappropriate antidiarrhetic hormone (ADH); obesity; infertility; head traumas; spinal cord trauma; ischemic neuronal damage (e.g., cerebral ischemia such as cerebral hippocampal ischemia); excitotoxic neuronal damage; epilepsy; cardiovascular and hear related disorders including hypertension, tachycardia and congestive heart failure; stroke; immune dysfunctions including stress induced immune dysfunctions (e.g., stress induced fevers, porcine stress syndrome, bovine shipping fever, equine paroxysmal fibrillation, and dysfunctions induced by confinement in chickens, sheering stress in sheep or human-animal interaction related stress in dogs); muscular spasms; urinary incontinence; senile dementia of the Alzheimer""s type; multiinfarct dementia; amyotrophic lateral sclerosis; chemical dependencies and addictions (e.g., dependencies on alcohol, cocaine, heroin, benzodiazepines, or other drugs); drug and alcohol withdrawal symptoms; osteoporosis; psychosocial dwarfism and hypoglycemia in mammals.
According to a still further aspect of the invention, the compounds provided by this invention (and especially labelled compounds of this invention) are also useful as standards and reagents in determining the ability of a potential pharmaceutical to bind to the CRF receptor.
[1] Thus, in a first embodiment, the present invention provides a novel compound of formula I: 
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
A is N or Cxe2x80x94R7;
B is N or Cxe2x80x94R8;
provided that at least one of the groups A and B is N;
D is an aryl or heteroaryl group attached through an unsaturated carbon atom;
X is selected from the group CHxe2x80x94R9, Nxe2x80x94R10, O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-4 alkoxy-C1-4 alkyl, xe2x80x94SO2xe2x80x94C1-10 alkyl, xe2x80x94SO2xe2x80x94R1a, and xe2x80x94SO2xe2x80x94R1b;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13a, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b;
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-4 alkoxy-C1-4 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than:
(a) a cyclohexyl-(CH2)2xe2x80x94 group;
(b) a 3-cyclopropyl-3-methoxypropyl group;
(c) an unsubstituted-(alkoxy)methyl group; and,
(d) a 1-hydroxyalkyl group;
also provided that when R1 alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH2;
R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, C2R14b, COR14b and SO2R14b;
R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR13a, SH, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94OC(O)R14b, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94NR13aR16a, and xe2x80x94CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl, xe2x80x94(CH2)1-4-heteroaryl, or xe2x80x94(CH2)1-4-heterocycle, wherein the aryl, heteroaryl, or heterocycle group is substituted or unsubstituted;
R2 is selected from the group C1-4 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-3 substituents selected from the group xe2x80x94CN, hydroxy, halo and C1-4 alkoxy;
alternatively R2, in the case where X is a bond, is selected from the group xe2x80x94CN, CF3 and C2F5;
R3, R7 and R8 are independently selected at each occurrence from the group H, Br, Cl, F, I, xe2x80x94CN, C1-4 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy less than , C1-4 alkylthio, C1-4 alkyl sulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2amino;
provided that when R1 is unsubstituted C1-10 alkyl, then R3 is other than substituted or unsubstituted phenyl;
R9 and R10 are independently selected at each occurrence from the group H, C1-4 alkyl, C3-6 cycloalkyl-C1-4 alkyl and C3-8 cycloalkyl;
R13 is selected from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)xe2x80x94, heteroaryl and heteroaryl(C1-4 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)xe2x80x94, heteroaryl and heteroaryl(C1-4 alkyl)xe2x80x94 and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
R14a is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R14b is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17 is selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, C1-4 haloalkyl, R14S(O)nxe2x80x94C1-4 alkyl, and R17bR19bNxe2x80x94C2-4 alkyl;
R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalky;
alternatively, In an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
alternatively, in an NR17bR19b moiety, R17b and R19b taken together form 1-pyrrolidinyl, 1-norpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkoxy-C1-4 alkoxy, xe2x80x94OR17, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94NO2, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CONR17R19, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C1-3 alkyl, C1-3 alkoxy, Br, Cl, F, I, xe2x80x94CN, dimethylamino, CF3, C2F5, OCF3, SC2Me and acetyl;
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CONR17R19, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a; and,
provided that when D is imidazole or triazole, R1 is other than unsubstituted C1-6 linear or branched alkyl or C3-6 cycloalkyl.
[2] In a preferred embodiment, the present invention provides a novel compound of formula Ia: 
[2a] In a more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-8 cycloalkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13a, xe2x80x94NCO2R14b, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-6 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R3 and R8 are independently selected at each occurrence from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[2b] In an even more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
X is selected from the group O, S and a bond;
R1 is substituted C1-6 alkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2R13a, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13a;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl which is substituted with 0-1 CH3 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SQ2CH3;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 and R8 are independently selected at each occurrence from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[2c] In a still more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is substituted C1;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2CH3, and xe2x80x94CO2CH2CH3;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2CH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, CH3-cyclopropyl, cyclobutyl, CH3-cyclobutyl, cyclopentyl, CH3-cyclopentyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 and R8 are independently selected at each occurrence from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[2d] In a further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is substituted (cyclopropyl)xe2x80x94C1 alkyl or (cyclobutyl)xe2x80x94C1 alkyl;
R1 is substituted with 0-1 xe2x80x94CN;
R1 is also substituted with 0-1 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2OH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[2e] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)xe2x80x94C1 alkyl substituted with 1 substituent independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1xe2x80x94CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, Cl, F, and CF3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atoms with a substituent independently selected at each occurrence from the group CH3, OCH3, Cl, F, and CF3.
[2f] In an even further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is selected from the group (cyclopropyl)CHxe2x80x94CH3, (cyclopropyl)CHxe2x80x94CH2CH3, (cyclpropyl)CHxe2x80x94CH2OCH3, (cyclopropyl)CHxe2x80x94CH2CH2CH3, (cycloppropyl)CHxe2x80x94CH2OCH3, (cyclopropyl)2CH, phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH, isoxazolyl(cyclopropyl)CH, (CH3-furanyl)(cyclopropyl)CH, (cyclobutyl)CHxe2x80x94CH3, (cyclobutyl)CHxe2x80x94CH2CH3, (cyclobutyl)CHxe2x80x94CH2OCH3, (cyclobutyl)CHxe2x80x94CH2CH2CH3, (cyclobutyl)CHxe2x80x94CH2CH2OCH3, (cyclobutyl)2CH, phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH, isoxazolyl(cyclobutyl)CH, and (CH3-furanyl)(cyclobutyl)CH;
[2g] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[2h] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[2i] In another preferred embodiment, the present invention provides a novel compound of formula Ia, wherein the compound is selected from the group:
3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-(methylsulfanyl)-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-(methylsulfanyl)-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-ethyl-7-[2-methyl-4-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-fluoro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methylphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo [4,5-b]pyridine;
7-(2-chloro-fluoro-4-methylphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-ethyl-7-(2,4,5-trimethylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-methoxy-7-(2,4,5-trimethylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-ethyl-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-2-methoxy-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-7-(2,6-dimethyl-3-pyridinyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
3-(1-cyclopropylpropyl)-7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(methylsulfonyl)phenyl]-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethylpropyl)-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-ethylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethylpropyl)-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;
3-(1-ethylpropyl)-2-methoxy-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine; 7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethylpropyl)-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethylpropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-ethylpropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
3-chloro-4-[2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridin-7-yl]benzonitrile;
3-chloro-4-[3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]benzonitrile;
1-{3-chloro-4-[2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;
1-{3-chloro-4-[3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;
3-(dicyclopropylmethyl)-2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(dicyclopropylmethyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-4-methoxyphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methoxyphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methoxyphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;
3-(1-ethyl-3-methoxypropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methylphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(methylsulfonyl)phenyl]-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
1-{3-chloro-4-[2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;
1-{3-chloro-4-[3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;
1-{5-[2-ethyl-3-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-b]pyridin-7-yl]-6-methyl-2-pyridinyl}-1-ethanone;
1-{5-[3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]-6-methyl-2-pyridinyl}-1-ethanone;
2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethoxy-3-pyridinyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethyl-3-pyridinyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(2,4-dichlorophenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-[1-(methoxymethyl)propyl]-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
2-methoxy-3-[1-(methoxymethyl)propyl]-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethoxy-3-pyridinyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
7-(2,6-dimethyl-3-pyridinyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
2-ethyl-3-[1-(methoxymethyl)propyl]-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
2-methoxy-3-[1-(methoxymethyl)propyl]-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;
7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine; and
7-[2-chloro-4-(methylsulfonyl)phenyl]-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;
or a pharmaceutically acceptable salt form thereof.
[2j]In another more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is C3-8 cycloalkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C4-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b; and,
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, C1-2 alkoxy-C1-2 alkyl, and xe2x80x94NR13aR16a.
[2k] In another even more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, and C4-8 cycloalkyl, wherein one carbon atom in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, C1-2 alkoxy-C1-2 alkyl, and xe2x80x94NR13aR16a;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R3 and R8 are independently selected at each occurrence from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R16, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[2l] In another still more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
X is selected from the group O, S and a bond;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2R13a, and C4-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF3, xe2x80x94OR13a, xe2x80x94OH, xe2x80x94OCH3, xe2x80x94OCH2CH3, xe2x80x94CH2OCH3, CH2CH2OCH3, and NR13aR16a;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 and R8 are independently selected at each occurrence from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[2m] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1xe2x80x94C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, and CF3;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 and R8 are independently selected at each occurrence from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[2n] In another even further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is substituted with 0-2 substituents independently selected at each occurrence from the group R1a, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, and CF3; and,
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[2o] In a still further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[2p] In another still further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[2q] In another more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 alkoxy-C1-4 alkyl;
R1 is substituted with a C3-8 cycloalkyl group, wherein 0-1 carbon atoms in the C4-8 cycloalkyl group is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2xe2x80x94, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b; and,
R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR13a, SH, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94OC(O)R14b, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94NR13aR16a, and xe2x80x94CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized.
[2r] In another even more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-8 cycloalkyl;
R1 is substituted with a C3-6 cycloalkyl group, wherein 0-1 carbon atoms in the C4-6 cycloalkyl group is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R3 and R8 are independently selected at each occurrence from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[2s] In another still more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
X is selected from the group O, S and a bond;
R1 is C1-6 alkyl;
R1 is substituted with a C3-6 cycloalkyl, wherein 0-1 carbon atoms in the C4-6 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, xe2x80x94CH2OCH3, CH2CH2OCH3 and C3-6 cycloalkyl which is substituted with 0-1 CH3 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 and R8 are independently selected at each occurrence from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCH3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[2t] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 1-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, CH3-cyclopropyl, cyclobutyl, CH3-cyclobutyl, cyclopentyl, CH3-cyclopentyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 and R8 are independently selected at each occurrence from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[2u] In another even further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 1-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[2v] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[2w] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[3] In another preferred embodiment, the present invention provides a novel compound of formula Ib: 
[3a] In another more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-8 cycloalkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R3 and R7 are independently selected at each occurrence from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OCO(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[3b] In another even more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
X is selected from the group O, S and a bond;
R1 is substituted C1-6 alkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2R13a, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl which is substituted with 0-1 CH3 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 and R7 are independently selected at each occurrence from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[3c] In another still more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is substituted C1;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2CH3, and xe2x80x94CO2CH2CH3;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, CH3-cyclopropyl, cyclobutyl, CH3-cyclobutyl, cyclopentyl, CH3-cyclopentyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 and R7 are independently selected at each occurrence from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, CO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[3d] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is substituted (cyclopropyl)xe2x80x94C1 alkyl or (cyclobutyl)xe2x80x94C1 alkyl;
R1 is substituted with 0-1 xe2x80x94CN;
R1 is also substituted with 0-1 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), Br, Cl, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1 is also substituted with 0-1 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2CH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[3e] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)xe2x80x94C1 alkyl substituted with 1 substituent independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, Cl, F, and CF3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atoms with a substituent independently selected at each occurrence from the group CH3, OCH3, Cl, F, and CF3.
[3f] In an even further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is selected from the group (cyclopropyl)CHxe2x80x94CH3, (cyclopropyl)CHxe2x80x94CH2CH3, (cyclopropyl)CHxe2x80x94CH2OCH3, (cyclopropyl)CHxe2x80x94CH2CH2CH3, (cyclopropyl)CHxe2x80x94CH2CH2OCH3, (cyclopropyl)2CH, phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH, isoxazolyl(cyclopropyl)CH, (CH3-furanyl)(cyclopropyl)CH, (cyclobutyl)CHxe2x80x94CH3, (cyclobutyl)CHxe2x80x94CH2CH3, (cyclobutyl)CHxe2x80x94CH2OCH3, (cyclobutyl)CHxe2x80x94CH2CH2CH3, (cyclobutyl)CHxe2x80x94CH2CH2OCH3, (cyclobutyl)2CH, phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH, isoxazolyl(cyclobutyl)CH, and (CH3-furanyl)(cyclobutyl)CH.
[3g] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[3h] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[3i] In another preferred embodiment, the present invention provides a novel compound of formula Ib, wherein the compound is selected from the group:
1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-ethyl-4-[2-methyl-4-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-(methylsulfanyl)-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-ethyl-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methylphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
2,4-(2-chloro-fluoro-4-methylphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-methoxy-4-(2,4,5-trimethylphenyl)-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-ethyl-4-(2,4,5-trimethylphenyl)-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-ethyl-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-2-methoxy-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-4-(2,6-dimethyl-3-pyridinyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
1-(1-cyclopropylpropyl)-4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(methylsulfonyl)phenyl]-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethylpropyl)-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;
1-(1-ethylpropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethylpropyl)-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;
1-(1-ethylpropyl)-2-methoxy-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;
1-(1-ethylpropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethylpropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;
3-chloro-4-[1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]benzonitrile;
3-chloro-4-[2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridin-4-yl]benzonitrile;
1-{3-chloro-4-[2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;.
1-{3-chloro-4-[1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;
1-(dicyclopropylmethyl)-2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;
1-(dicyclopropylmethyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methoxyphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;
1-(1-ethyl-3-methoxypropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methylphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(methylsulfonyl)phenyl]-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
1-{3-chloro-4-[1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;
1-{3-chloro-4-[2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;
1-{5-[1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]-6-methyl-2-pyridinyl}-1-ethanone;
1-{5-[2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridin-4-yl]-6-methyl-2-pyridinyl}-1-ethanone;
1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethoxy-3-pyridinyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethyl-3-pyridinyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(2,4-dichlorophenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
2-ethyl-4-(4-methoxy-2,5-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
2-methoxy-1-[1-(methoxymethyl)propyl]-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-[1-(methoxymethyl)propyl]-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethoxy-3-pyridinyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
4-(2,6-dimethyl-3-pyridinyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
2-ethyl-1-[1-(methoxymethyl)propyl]-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
2-methoxy-1-[1-(methoxymethyl)propyl]-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;
4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine; and
4-[2-chloro-4-(methylsulfonyl)phenyl]-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;
or a pharmaceutically acceptable salt form thereof.
[3j] In another more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is C3-8 cycloalkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C4-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b; and,
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, C1-2 alkoxy-C1-2 alkyl, and xe2x80x94NR13aR16a.
[3k] In another even more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, and C4-8 cycloalkyl, wherein one carbon atom in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, NCO2R14bxe2x80x94, NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, C1-2 alkoxy-C1-2 alkyl, and xe2x80x94NR13aR16a;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R3 and R7 are independently selected at each occurrence from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[3l] In another still more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
X is selected from the group O, S and a bond;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2R13a, and C4-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94; 
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C16 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF3, xe2x80x94OR13a, xe2x80x94OH, xe2x80x94OCH3, xe2x80x94OCH2CH3, xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, and xe2x80x94NR13aR16a;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3; R15, CO2R14a, COR14a and SO2R14a.
R3 and R7 are independently selected at each occurrence from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[3m] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2OH2OCH3, F, and CF3;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 and R7 are independently selected at each occurrence from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[3n] In another even further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is substituted with 0-2 substituents independently selected at each occurrence from the group R1a, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, and CF3; and,
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[3o] In another still further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[3p] In another still further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[3q] In another more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 alkoxy-C1-4 alkyl;
R1 is substituted with a C3-8 cycloalkyl group, wherein 0-1 carbon atoms in the C4-8 cycloalkyl group is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13a, xe2x80x94NCO2R14b, xe2x80x94NCOR14bxe2x80x94 and SO2R14bxe2x80x94.
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxyC1-2 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b; and,
R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR13a, SH, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94OC(O)R14b, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94NR13aR16a, and CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized.
[3r] In another even more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl;
R1 is substituted with a C3-6 cycloalkyl group, wherein 0-1 carbon atoms in the C4-6 cycloalkyl group is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and R17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R3 and R7 are independently selected at each occurrence from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a;
[3s] In another still more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
X is selected from the group O, S and a bond;
R1 is C1-6 alkyl;
R1 is substituted with a C3-6 cycloalkyl, wherein 0-1 carbon atoms in the C4-4 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, xe2x80x94CH2CH3, xe2x80x94CH2CH2OCH3, and C3-6 cycloalkyl which is substituted with 0-1 CH3 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 and R7 are independently selected at each occurrence from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2OH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[3t] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 1-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, CH3-cyclopropyl, cyclobutyl, CH3-cyclobutyl, cyclopentyl, CH3-cyclopentyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 and R7 are independently selected at each occurrence from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[3u] In another even further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 1-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[3v] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[3w] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[4] In another preferred embodiment, the present invention provides a novel compound of formula Ic: 
[4a] In another more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-8 cycloalkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14b, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R3 is selected from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[4b] In another even more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
X is selected from the group O, S and a bond;
R1 is substituted C1-6 alkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2R13a, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C2 alkyl, and C3-6 cycloalkyl which is substituted with 0-1 CH3 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 is selected from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[4c] In another still more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is substituted C1;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94CO2CH3, and xe2x80x94CO2CH2CH3;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2OH2OCH3, F, CF3, cyclopropyl, CH3-cyclopropyl, cyclobutyl, CH3-cyclobutyl, cyclopentyl, CH3-cyclopentyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO02CH3, COCH3 and SO2CH3;
provided that R1 is other than a xe2x80x94(CH2)1-4-aryl or xe2x80x94(CH2)1-4-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 is selected from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[4d] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is substituted (cyclopropyl)xe2x80x94C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 0-1 xe2x80x94CN;
R1 is also substituted with 0-1 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2OH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[4e] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)xe2x80x94C1 alkyl substituted with 1 substituent independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2,CH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, Cl, F, and CF3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atoms with a substituent independently selected at each occurrence from the group CH3, OCH3, Cl, F, and CF3.
[4f] In an even further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is selected from the group (cyclopropyl)CHxe2x80x94CH3, (cyclopropyl)CHxe2x80x94CH2CH3, (cyclopropyl)CHxe2x80x94CH2OCH3, (cyclopropyl)CHxe2x80x94CH2CH2CH3, (cyclopropyl)CHxe2x80x94CH2CH2OCH3, (cyclopropyl)2CH, phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH, isoxazolyl(cyclopropyl)CH, (CH3-furanyl)(cyclopropyl)CH, (cyclobutyl)CHxe2x80x94CH3, (cyclobutyl)CHxe2x80x94CH2CH3, (cyclobutyl)CHxe2x80x94CH2OCH3, (cyclobutyl)CHxe2x80x94CH2CH2CH3, (cyclobutyl)CHxe2x80x94OH2C2OCH3, (cyclobutyl)2CH, phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH, isoxazolyl(cyclobutyl)CH, and (CH3-furanyl)(cyclobutyl)CH.
[4g] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[4h] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[4i] In another preferred embodiment, the present invention provides a novel compound of formula Ic, wherein the compound is selected from the group:
6-(2,4-bis(trifluoromethyl)phenyl-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-cyanophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methoxy-5-chlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methoxy-5-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(2-hexyl)-9H-purine;
6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;
6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(3-heptyl)-9H-purine;
6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(3-hexyl)-9H-purine;
6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;
6-(2-chloro-4-methoxyphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methoxyphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methoxyphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methoxyphenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;
6-(2-chloro-4-methyl-5-fluorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;
6-(2-chloro-4-methylphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;
6-(2-chloro-4-methylphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;
6-(2-chloro-4-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethoxyphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;
6-(2-chloro-4-trifluoromethoxyphenyl)-8-ethyl-9-(3-hexyl)-9H-purine;
6-(2-chloro-4-trifluoromethoxyphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethoxyphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethoxyphenyl)-9(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-hexyn-3-yl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-pentyn-3-yl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-pentyn-4-yl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-phenyl-2-butynyl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-heptyn-4-yl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-hexyn-4-yl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-[(2-furanyl)-cyclopropylmethyl]-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-[1-(2-furanyl)propyl]-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclobutylethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropyl-2-butynyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropyl-2-propenyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;
6-(2-chloro-4-trifluoromethylphenyl)-9-[1-cyclopropyl-1-(2-thienyl)methyl]-8-ethyl-9H-purine;
9-(1-cyclobutylethyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-[1-cyclopropyl-(3-methylisoxazol-5-yl)methyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropyl-2-butynyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropyl-2-butynyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropyl-2-propenyl)-6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9H-purine;
9-(1-cyclopropyl-2-propenyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropyl-2-propynyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
9-(1-cyclopropyl-4xe2x80x2-fluorobenzyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropylbenzyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropylbenzyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
9-(1-cyclopropylbutyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropylbutyl)-8-ethyl-6-(2,4,6-trimethylphenyl)-9H-purine;
9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;
9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4-chlorophenyl)-9H-purine;
9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;
9-(1-cyclopropylbutyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;
9-(1-cyclopropylbutyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
9-(1-cyclopropylethyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropylethyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;
9-(1-cyclopropylpentyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;
9-(1-cyclopropylpropyl)-6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9H-purine;
9-(1-cyclopropylpropyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;
9-(1-cyclopropylpropyl)-8-ethyl-6-(2,4,6-trimethylphenyl)-9H-purine;
9-(1-cyclopropylpropyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;
6-(2,4-dichloro-5-fluorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9-(2-penten-3-yl)-9H-purine;
6-(2,4-dichloro-6-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(1-hexyn-3-yl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(1-methoxycarbonylpropyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(1-phenyl-2-butynyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(2-heptyn-4-yl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(2-hexyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(2-hexyn-4-yl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(2-penten-3-yl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(2-pentyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(3-heptyl)-9H-purine;
6-(2,4-.dichlorophenyl)-8-ethyl-9-(3-hexyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(3-pentyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-(4-heptyl)-9H-purine;
6-(2,4-dichlorophenyl)-8-ethyl-9-[1-(2-methylcyclopropyl)ethyl]-9H-purine;
6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;
6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;
6-(2,4-dichlorophenyl)-9-(diphenylmethyl)-8-ethyl-9H-purine;
9-(dicyclopropylmethyl)-6-(2,4-dimethylphenyl)-8-ethyl-9H-purine;
9-(dicyclopropylmethyl)-6-(2,4-dimethylphenyl)-8-ethyl-9H-purine;
9-(dicyclopropylmethyl)-6-(2,6-dimethoxypyridin-3-yl)-8-methoxy-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2,4,5-trichlorophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methoxy-4-trifluoromethylphenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-chlorophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-dimethylaminophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxy-5-chlorophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxy-5-fluorophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-chloro-4-methoxy-5-fluorophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-propyloxyphenyl)-9H-purine;

6-(2,6-dimethoxypyridin-3-yl)-8-ethyl-9-(2-pentyl)-9H-purine;
6-(2,4-dimethylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;
8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9-(2-pentyl)-9H-purine;
8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9-(3-pentyl)-9H-purine;
8-ethyl-9-(1-hexen-3-yl)-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;
8-ethyl-9-(1-hexen-3-yl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
8-ethyl-9-(2-hexyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
8-ethyl-9-(2-pentyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
8-ethyl-9-(3-hexyl)-6-(2-methyl-4-methoxyphenyl)-9H-purine;
8-ethyl-9-(3-hexyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;
8-ethyl-9-(3-pentyl)-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;
8-ethyl-9-(4-heptyl)-6-(2-methyl-4-chlorophenyl)-9H-purine;
8-ethyl-9-(4-heptyl)-6-(2-methyl-4-methoxyphenyl)-9H-purine;
8-ethyl-9-(4-heptyl)-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;
8-ethyl-9-(4-b eptyl)-6-(2-trifluoromethyl-4 methoxyphenyl)-9H-purine; and
9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-6-methoxy-3-pyridyl)-9H-purine;
or a pharmaceutically acceptable salt form thereof.
[4j] In another more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is C3-8 cycloalkyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C4-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b; and,
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, C1-2 alkoxy-C1-2 alkyl, and xe2x80x94NR13aR16a.
[4k] In another even more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, and C4-8 cycloalkyl, wherein one carbon atom in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, C1-2 alkoxy-C1-2 alkyl, and xe2x80x94NR13aR16a;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R3 is selected from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14,
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[4l] In another still more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
X is selected from the group C, S and a bond;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, OC2R13a, and C4-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF3, xe2x80x94OR13a, xe2x80x94OH, xe2x80x94OCH3, xe2x80x94OCH2CH3, xe2x80x94OH2OCH3, xe2x80x94CH2CH2CH3, and NR13aR16a;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 is selected from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(Q)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[4m] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, and CF3;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 is selected from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[4n] In another even further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is substituted with 0-2 substituents independently selected at each occurrence from the group R1a, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, and CF3; and,
R1a is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[4o] In another still further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[4p] In another still further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[4q] In another more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 alkoxy-C1-4 alkyl;
R1 is substituted with a C3-8 cycloalkyl group, wherein 0-1 carbon atoms in the C4-8 cycloalkyl group is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13a, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94;
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R, xe2x80x94NR17aR19a and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b; and,
R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR13a, SH, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94OC(O)R14b, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94NR13aR16a, and xe2x80x94CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized.
[4r] In another even more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
X is selected from the group O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-8 cycloalkyl;
R1 is substituted with a C3-6 cycloalkyl group, wherein 0-1 carbon atoms in the C4-6 cycloalkyl group is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, CF3, CF2CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
R1a is aryl and is selected from the group phenyl and indanyl, each R1a being substituted with 0-1 xe2x80x94OR17 and 0-5 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, Br, Cl, F, CF3, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R2 is selected from the group C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-1 substituents selected from the group xe2x80x94CN, OH, Cl, F, and C1-4 alkoxy;
R9 is independently selected at each occurrence from the group H, C1-4 alkyl and C3-8 cycloalkyl;
R3 is selected from the group H, Br, Cl, F, xe2x80x94CN, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, NH2, C1-4 alkylamino, and (C1-4 alkyl)2-amino;
R13 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl-C1-2 alkyl, aryl(C1-2 alkyl)xe2x80x94, and heteroaryl(C1-2 alkyl)xe2x80x94;
R14a is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R14b is selected from the group C1-4 alkyl, C1-2 haloalkyl, C1-2 alkoxy-C1-2 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-2 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17, R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C1-4 alkyl, C3-6 cycloalkyl, xe2x80x94OR17, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94NR15COR17, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94OR17, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a;
[4s] In another still more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
X is selected from the group O, S and a bond;
R1 is C1-6 alkyl;
R1 is substituted with a C3-6 cycloalkyl, wherein 0-1 carbon atoms in the C4-4 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, and xe2x80x94NR13axe2x80x94;
R1 is also substituted with 0-2 substituents independently selected at each occurrence from the group R1a, R1b, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, CF3, xe2x80x94OR13a, xe2x80x94NR13aR16a, xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, and C3-6 cycloalkyl which is substituted with 0-1 CH3 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than a cyclohexyl-(CH2)2xe2x80x94 group;
R1a is aryl and is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, and OCF3, and 0-3 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
R3 is selected from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(C)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3.
[4t] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 1-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, CH3-cyclopropyl, cyclobutyl, CH3-cyclobutyl, cyclopentyl, CH3-cyclopentyl;
R1a is phenyl substituted with 0-1 substituents selected from OCH3, OCH2CH3, and OCF3, and 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH3, CO2CH3, COCH3 and SO2CH3;
R2 is selected from the group CH3, CH2CH3, and CH(CH3)2;
R3 is selected from the group H and CH3;
aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2; and,
heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, SCH3, SO2CH3, xe2x80x94NH2, xe2x80x94NHCH3, xe2x80x94N(CH3)2, xe2x80x94C(O)NH2, xe2x80x94C(O)NHCH3, and xe2x80x94C(O)N(CH3)2.
[4u] In another even further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
R1 is (cyclopropyl)C1 alkyl or (cyclobutyl)C1 alkyl;
R1 is substituted with 1-2 substituents independently selected at each occurrence from the group R1a, R1b, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, xe2x80x94(CH2)3CH3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CH(CH3), xe2x80x94CHxe2x89xa1CH, xe2x80x94CHxe2x89xa1C(CH3), xe2x80x94CH2OCH3, xe2x80x94CH2CH2OCH3, F, CF3, cyclopropyl, and CH3-cyclopropyl;
R1a is-phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3;
R1b is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, OCH3, OCH2CH3, OCF3, Br, Cl, F, CF3, xe2x80x94CN, and SCH3.
[4v] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[4w] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:
D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cyclopropyl, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, OCF3, Br, Cl, F, and CF3.
[5l] In a third embodiment, the present invention provides a novel pharmaceutical composition, comprising: a pharmaceutically acceptable carrier arid a therapeutically effective amount of a compound of formula (I): 
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
A is N or Cxe2x80x94R7;
B is N or Cxe2x80x94R8;
provided that at least one of the groups A and B is N;
D is an aryl or heteroaryl group attached through an unsaturated carbon atom;
X is selected from the group CHxe2x80x94R9, Nxe2x80x94R10, O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-4 alkoxy-C1-4 alkyl, xe2x80x94SO2xe2x80x94C1-10 alkyl, xe2x80x94SO2xe2x80x94R1a, and xe2x80x94SO2xe2x80x94R1b;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13axe2x80x94, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14bxe2x80x94 and xe2x80x94NSO2R14bxe2x80x94 and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b;
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, xe2x80x94NR13aR16a, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than:
(a) a 3-cyclopropyl-3-methoxypropyl group;
(b) an unsubstituted-(alkoxy)methyl group; and,
(c) a 1-hydroxyalkyl group;
also provided that when R1 alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH2;
R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR13a, SH, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94OC(O)R14b, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94NR13aR16a, and xe2x80x94CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized;
R2 is selected from the group C1-4 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-3 substituents selected from the group xe2x80x94CN, hydroxy, halo and C1-4 alkoxy;
alternatively R2, in the case where X is a bond, is selected from the group xe2x80x94CN, CF3 and C2F5;
R3, R7 and R8 are independently selected at each occurrence from the group H, Br, Cl, F, I, xe2x80x94CN, C1-4 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio, C1-4 alkyl sulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2amino;
provided that when R1 is unsubstituted C1-1 o alkyl, then R3 is other than substituted or unsubstituted phenyl;
R9 and R10 are independently selected at each occurrence from the group H, C1-4 alkyl, C3-8 cycloalkyl-C1-4 alkyl and C3-8 cycloalkyl;
R13 is selected from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)xe2x80x94, heteroaryl and heteroaryl(C1-4 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)xe2x80x94, heteroaryl and heteroaryl(C1-4 alkyl)xe2x80x94 and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
R14a is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R14b is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17 is selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, C1-4 haloalkyl, R14S(O)nxe2x80x94C1-4 alkyl, and R17bR19bNxe2x80x94C2-4 alkyl;
R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
alternatively, in an NR17bR19b moiety, R17b and R19b taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkoxy-C1-4 alkoxy, xe2x80x94OR17, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94NO2, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CONR17R19, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C1-3 alkyl, C1-3 alkoxy, Br, Cl, F, I, xe2x80x94CN, dimethylamino, CF3, C2F5, OCF3, SO2Me and acetyl; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CONR17R19, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
[6] In a second embodiment, the present invention provides a novel method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer""s disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of formula (I): 
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
A is N or Cxe2x80x94R7;
B is N or Cxe2x80x94R8;
provided that at least one of the groups A and B is N;
D is an aryl or heteroaryl group attached through an unsaturated carbon atom;
X is selected from the group CHxe2x80x94R9, Nxe2x80x94R10, O, S(O)n and a bond;
n is 0, 1 or 2;
R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-4 alkoxy-C1-4 alkyl, xe2x80x94SO2xe2x80x94C1-10 alkyl, xe2x80x94SO2xe2x80x94R1a, and xe2x80x94SO2xe2x80x94R1b;
R1 is substituted with 0-1 substituents selected from the group xe2x80x94CN, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94CO2R13a, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group xe2x80x94Oxe2x80x94, xe2x80x94S(O)nxe2x80x94, xe2x80x94NR13a, xe2x80x94NCO2R14bxe2x80x94, xe2x80x94NCOR14xe2x80x94 and xe2x80x94NSO2R14bxe2x80x94, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b;
R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94OR13a, xe2x80x94NR13aR16a, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by xe2x80x94Oxe2x80x94;
provided that R1 is other than:
(a) a 3-cyclopropyl-3-methoxypropyl group;
(b) an unsubstituted-(alkoxy)methyl group; and,
(c) a 1-hydroxyalkyl group;
also provided that when R1 alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH2;
R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R8, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a;
R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C16 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94OC(O)R18, xe2x80x94NR15aCOR17, xe2x80x94N(COR17)2, xe2x80x94NR15aCONR17aR19a, xe2x80x94NR15aCO2R18, xe2x80x94NR17aR19a, and xe2x80x94CONR17aR19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b;
R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR13a, SH, xe2x80x94S(O)nR14b, xe2x80x94COR13a, xe2x80x94OC(O)R14b, xe2x80x94NR15aCOR13a, xe2x80x94N(COR13a)2, xe2x80x94NR15aCONR13aR16a, xe2x80x94NR15aCO2R14b, xe2x80x94NR13aR16a, and xe2x80x94CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized;
R2 is selected from the group C1-4 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-3 substituents selected from the group xe2x80x94CN, hydroxy, halo and C1-4 alkoxy;
alternatively R2, in the case where X is a bond, is selected from the group xe2x80x94CN, CF3 and C2F5;
R3, R7 and R8 are independently selected at each occurrence from the group H, Br, Cl, F, I, xe2x80x94CN, C1-4 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio, C1-4 alkyl sulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2amino;
provided that when R1 is unsubstituted C1-10 alkyl, then R3 is other than substituted or unsubstituted phenyl;
R9 and R10 are independently selected at each occurrence from the group H, C1-4 alkyl, C3-6 cycloalkyl-C1-4 alkyl and C3-8 cycloalkyl;
R13 is selected from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)xe2x80x94, heteroaryl and heteroaryl(C1-4 alkyl)xe2x80x94;
R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R14 is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)xe2x80x94, heteroaryl and heteroaryl(C1-4 alkyl)xe2x80x94 and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
R14a is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R14b is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl;
R17 is selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, C1-4 haloalkyl, R14S(O)nxe2x80x94C1-4 alkyl, and R17bR19bNxe2x80x94C2-4 alkyl;
R18 and R19 are independently selected at each occurrence form the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl;
alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein, N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
alternatively, in an NR17bR19b moiety, R17b and R19b taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein, N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14;
R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl;
aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl R13, CO2R14, COR14 and SO2R14; being substituted with 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkoxy-C1-4 alkoxy, xe2x80x94OR17, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, xe2x80x94NO2, SH, xe2x80x94S(O)nR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CONR17R19, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C1-3 alkyl, C1-3 alkoxy, Br, Cl, F, I, xe2x80x94CN, dimethylamino, CF3, C2F5, OCF3, SO2Me and acetyl; and,
heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, xe2x80x94CN, nitro, xe2x80x94OR17, SH, xe2x80x94S(O)mR18, xe2x80x94COR17, xe2x80x94CO2R17, xe2x80x94OC(O)R18, xe2x80x94NR15COR17, xe2x80x94N(COR17)2, xe2x80x94NR15CONR17R19, xe2x80x94NR15CO2R18, xe2x80x94NR17R19, and xe2x80x94CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a.
In another preferred embodiment, R1 is other than a cyclohexyl-(CH2)1, 2, 3, 4, 5, 6, 7, 8, 9, or 10xe2x80x94 group.
In another preferred embodiment, R1 is other than an aryl-(CH2)1, 2, 3, 4, 5, 6, 7, 8, 9, or 10xe2x80x94 group, wherein the aryl group is substituted or unsubstituted.
In another preferred embodiment, R1 is other than a heteroaryl-(CH2)1, 2, 3, 4, 5, 6, 7, 8, 9, or 10xe2x80x94 group, wherein the heteroaryl group is substituted or unsubstituted.
In another preferred embodiment, R1 is other than a heterocyclyl-(CH2)1, 2, 3, 4, 5, 6, 7, 8, 9, or 10xe2x80x94 group, wherein the heterocyclyl group is substituted or unsubstituted.
In another preferred embodiment, when D is imidazole or triazole, R1 is other than unsubstituted C1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 linear or branched alkyl or C3, 4, 5, 6, 7, or 8 cycloalkyl.
In another preferred embodiment, R1a is not substituted with OR17.
Many compounds of this invention have one or more asymmetric centers or planes. Unless otherwise indicated, all chiral (enantiomeric and diastereomeric) and racemic forms are included in the present invention. Many geometric isomers of olefins, Cxe2x95x90N double bonds, and the like can also be present in the compounds, and all such stable isomers are contemplated in the present invention. The compounds may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All chiral, (enantiomeric and diastereomeric) and racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated. The term xe2x80x9calkylxe2x80x9d includes both branched and straight-chain alkyl having the specified number of carbon atoms. xe2x80x9cAlkenylxe2x80x9d includes hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl, and the like. xe2x80x9cAlkynylxe2x80x9d includes hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl and the like. xe2x80x9cHaloalkylxe2x80x9d is intended to include both branched and straight-chain alkyl having the specified number of carbon atoms, substituted with 1 or more halogen; xe2x80x9calkoxyxe2x80x9d represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge; xe2x80x9ccycloalkylxe2x80x9d is intended to include saturated ring groups, including mono-,bi- or polycyclic ring systems, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and so forth. xe2x80x9cHaloxe2x80x9d or xe2x80x9chalogen, includes fluoro, chloro, bromo, and iodo.
The term ""substitutedxe2x80x9d, as used herein, means that one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom""s normal valency is not exceeded, and that the substitution results in a stable compound. When a substitent is keto (i.e., xe2x95x90O), then 2 hydrogens on the atom are replaced.
Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. By xe2x80x9cstable compoundxe2x80x9d or xe2x80x9cstable structurexe2x80x9d is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.
The term xe2x80x9cpharmaceutically acceptable saltsxe2x80x9d includes acid or base salts of the compounds of formulas (I) and (II). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like.
Pharmaceutically acceptable salts of the compounds of the invention can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Reminaton""s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference.
xe2x80x9cProdrugsxe2x80x9d are considered to be any covalently bonded carriers which release the active parent drug of formula (I) or (II) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the compounds of formula (I) and (II) are prepared by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compounds. Prodrugs include compounds wherein hydroxy, amine, or sulfhydryl groups are abonded to any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino, or sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formulas (I) and (II); and the like.
The term xe2x80x9ctherapeutically effective amountxe2x80x9d of a compound of this invention means an amount effective to antagonize abnormal level of CRF or treat the symptoms of affective disorder, anxiety, depression, immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in a host.